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Влияние введения смеси фосфотидилхолинов на состояние кортикального цитоскелета волокон камбаловидной мышцы крысы
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Огнева И. В.
Свистунов А.А.
Несвижский Юрий Владимирович
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Авиакосмическая и экологическая медицина |
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Цель работы - оценка состояния кортикального цитоскелета волокон камбаловидной мышцы крысы в результате 6-часового антиортостатического вывешивания на фоне предшествующего, в течение 3 сут по 100 мкг/сут, введения смеси фосфатидилхолинов (лецитина). Данные о периметре волокон, толщине подмембранного цитоскелета и доле разрывов в нем относительно периметра получали, используя иммуногистохимическую окраску на альфа-актинин-4. Периметр волокон оставался неизменным во всех группах исследования. При этом доля разрывов была выше в группах вывешивания, чем в соответствующих контрольных группах. Толщина окрашенного слоя, соответствующего подмембранному цитоскелету, не менялась в контрольных группах и в группе вывешивания без лецитина, однако в группе вывешивания на фоне лецитина она достоверно увеличивалась по сравнению с соответствующей контрольной группой на 27 % (p < 0,05) соответственно.
Purpose of the work was to assess the cortical cytoskeleton of m. soleus fibers from rats after 6-hr tail-suspension preceded by 3 days of phosphatidylcholine (lecithin) injections at a dose of 100 µг/d. Data about the fiber perimeter, submembrane cytoskeleton thickness and percentage of bonds breaks along the perimeter were obtained using the alpha-actinin-4 anti-body stain. The fiber perimeter remained unchanged in all groups under study. However, the percentage of breaks was high in suspension groups but not in respective groups of control. Thickness of the stained layer commensurate to the submembrane cytoskeleton did not change in the control groups and in the suspension group without lecithin injections but increased reliably in the suspension group that recieved injections by 27 % (p < 0.05) in comparison with its control.
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Публикация |
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Similarity of female central (hypogonadotropic) hypogonadism and postmenopause
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Зекцер В.Ю.
Свистунов А.А.
Несвижский Юрий Владимирович
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Climacteric |
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Objectives: Central (hypogonadotropic) hypogonadism in women could be a cause of persistent amenorrhea and hypoestrogenemia as observed in postmenopause. This study aimed to compare the clinical, hormonal and biochemical features in women with non-physiological (central hypogonadism) and physiological (postmenopause) hypoestrogenemia.
Methods: A total of 161 young women, median age 24.9 years (interquartile range (IQR) 21.2; 30.5) with central hypogonadism (with isolated hypogonadotropic hypogonadism, n = 76, and with hypopituitarism, n = 85), 53 healthy young women, median age 23.9 years (IQR 23.1; 28.0) and 50 healthy postmenopausal women, median age 56.0 years (IQR 53.1; 58.5), were examined. Psychoemotional, neurovegetative and urogenital symptoms, sex steroid levels, parameters of lipid and mineral metabolism were evaluated.
Results: In young women with central hypogonadism, the frequencies of psychoemotional, neurovegetative and urogenital complaints differed significantly from those in healthy young women and were similar to those in postmenopausal women. Concentrations of estradiol, testosterone, dehydroepiandrosterone sulfate, parameters of lipid and mineral metabolism as well as quality of life in women with central hypogonadism were not typical of healthy young women but were similar to those of postmenopausal women of middle/old age.
Conclusions: Despite the young age of women with central hypogonadism, clinical, hormonal and biochemical abnormalities were similar in many aspects to those in postmenopausal women at middle/old age. These revealed features could be considered as signs of premature aging in young amenorrheic women with low gonadotropin levels.
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Публикация |
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Bilayer permeability during phase transition as an Erlang flow of hydrophilic pores resulting from diffusion in the radius space
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Аносов Андрей Анатольевич
Смирнова Елена Юрьевна
Несвижский Юрий Владимирович
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Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology |
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The formation of hydrophilic pores in lipid bilayer during phase transition is described using Smolukhowski's equation with an additional term of the hydrophobic pore source. This term is added to account for defects in lipid packing during phase transition. We assume that the temporal sequence of the pores is a stochastic process, a non -stationary second- order Erlang flow. Flow characteristics depend on the equation solution and determine the formation times of the hydrophilic pore. The calculated distribution of the durations of intervals between hydrophilic pore formations is in a good agree ment with experimental data published before. In terms of this model we describe the influence of poly (ethylene glycol) on the pore formation frequency.
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PUBMED DOI |
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Single Mutation in Peptide Inhibitor of TRPV1 Receptor Changes Its Effect from Hypothermic to Hyperthermic Level in Animals
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Андреев Я. А.
Логашина Ю. А.
Несвижский Юрий Владимирович
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Russian Journal of Bioorganic Chemistry |
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The TRPV1 receptor plays a significant role in many biological processes, such as perception of external temperature (above 43°C), inflammation development, and thermoregulation. Activation of TRPV1 leads to the pain occurrence and decrease in the body temperature, while inhibition of this receptor can lead to an increase in the temperature. The TRPV1 peptide modulators from sea anemone Heteractis crispa extract (APHC1 and APHC3) have been previously characterized as molecules, which generated a pronounced analgesic effect and a decrease in the body temperature in experimental animals. Using the combined APHC1 and APHC3 amino acid sequences, we have prepared a hybrid peptide molecule named A13 that contains all residues potentially important for the activity of the peptide precursors. Biological tests on animals have shown that the hybrid molecule not only combines the analgesic properties of both peptides but, unlike the peptide precursors, also raises the body temperature of experimental animals.
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Публикация |
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A scientific methodology for expansion of anti-parkinson drug product range
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Пятигорская Наталья Валерьевна
Бркич Галина Эдуардовна
Несвижский Юрий Владимирович
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Journal of Pharmaceutical Sciences and Research |
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A Scientific Methodology for Expansion of Anti-Parkinson Drug Product Range Nat a lia Valeryevna Pyatigorskaya Galina Eduardovna Brkich Alexey Nikitich Pavlov Valery Vasilyevich Beregovykh Olga Vladimirovna Evdokimova Sechenov First Moscow State Medical University, Russian Fedetation, 119991, Moscow, Trubetskaya Street, 8-2 Abstract Parkinson's disease (PD) is a chronic and progressive brain disease associat ed primarily with dopamine neurons degeneration of substantia nigra. More than 10 millions of people worldwide are affected by this disease manifested by combination of hypokinesia and rigidity, shaking, and postural instability. The high prevalence of disease has determined the aim of the study: to deve lop a methodology for expansion of anti-Parkinson drug product range. The information analysis methods were used for unbiased evaluation of novel anti-Parkinson drugs creation prospects. A systemic analysis of active pharmaceu tical ingredients (AFIs) used in anti- Parkinson drug products allowed for discovery of most widely used, levodopa being the top one. A comparative assessment of dosage forms used in Parkinson’s disease treatment showed th at they are represented primarily by intestinal gels, tablets, dispersible tablets, capsules, and modified release capsules. The authors conclude, that the novel anti-Parkinson drug pr oduct should contain levodopa in form of an endonasal spray which provides optimal bioavailability due to neces sary excipients (triglycerides, sodium monohydrogen phosphate, volatile and fatty oils, herbal extracts, stabilizers, and flavouring agents).
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Публикация |
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Indispensable Role of Proteases in Plant Innate Immunity
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Замятнин Андрей Александрович
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International Journal of Molecular Sciences |
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Plant defense is achieved mainly through the induction of microbe-associated molecular patterns (MAMP)-triggered immunity (MTI), effector-triggered immunity (ETI), systemic acquired resistance (SAR), induced systemic resistance (ISR), and RNA silencing. Plant immunity is a highly complex phenomenon with its own unique features that have emerged as a result of the arms race between plants and pathogens. However, the regulation of these processes is the same for all living organisms, including plants, and is controlled by proteases. Different families of plant proteases are involved in every type of immunity: some of the proteases that are covered in this review participate in MTI, affecting stomatal closure and callose deposition. A large number of proteases act in the apoplast, contributing to ETI by managing extracellular defense. A vast majority of the endogenous proteases discussed in this review are associated with the programmed cell death (PCD) of the infected cells and exhibit caspase-like activities. The synthesis of signal molecules, such as salicylic acid, jasmonic acid, and ethylene, and their signaling pathways, are regulated by endogenous proteases that affect the induction of pathogenesis-related genes and SAR or ISR establishment. A number of proteases are associated with herbivore defense. In this review, we summarize the data concerning identified plant endogenous proteases, their effect on plant-pathogen interactions, their subcellular localization, and their functional properties, if available, and we attribute a role in the different types and stages of innate immunity for each of the proteases covered. View Full-Text
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Публикация |
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Pro-neurogenic, Memory-Enhancing and Anti-stress Effects of DF302, a Novel Fluorine Gamma-Carboline Derivative with Multi-target Mechanism of Action
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Петер Леш
Стрекалова Т.В.
Умрюхин А.T.
Баженова Н.С.
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Molecular Neurobiology |
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A comparative study performed in mice investigating the action of DF302, a novel fluoride-containing gamma-carboline derivative, in comparison to the structurally similar neuroprotective drug dimebon. Drug effects on learning and memory, emotionality, hippocampal neurogenesis and mitochondrial functions, as well as AMPA-mediated currents and the 5-HT6 receptor are reported. In the step-down avoidance and fear-conditioning paradigms, bolus administration of drugs at doses of 10 or 40 mg/kg showed that only the higher dose of DF302 improved long-term memory while dimebon was ineffective at either dosage. Short-term memory and fear extinction remained unaltered across treatment groups. During the 5-day predation stress paradigm, oral drug treatment over a period of 2 weeks at the higher dosage regimen decreased anxiety-like behaviour. Both compounds supressed inter-male aggression in CD1 mice, the most eminent being the effects of DF302 in its highest dose. DF302 at the higher dose decreased floating behaviour in a 2-day swim test and after 21-day ultrasound stress. The density of Ki67-positive cells, a marker of adult neurogenesis, was reduced in the dentate gyrus of stressed dimebon-treated and non-treated mice, but not in DF302-treated mice. Non-stressed mice that received DF302 had a higher density of Ki67-positive cells than controls unlike dimebon-treated mice. Similar to dimebon, DF302 effectively potentiated AMPA receptor-mediated currents, bound to the 5-HT6 receptor, inhibited mitochondrial permeability transition and displayed cytoprotective properties in cellular models of neurodegeneration. Thus, DF302 exerts multi-target effects on the key mechanisms of neurodegenerative pathologies and can be considered as an optimized novel analogue of the neuroprotective agent dimebon.
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Recombination in the rabies virus and other lyssaviruses
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Девяткин Андрей Андреевич
Лукашев Александр Николаевич
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Infection, Genetics and Evolution |
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Recombination is a common event in RNA viruses; however, in the rabies virus there have been only a few reports of isolated recombination events. Comprehensive analysis found traces of recent recombination events within Arctic, Arctic-like and Africa 1b rabies virus groups, as well as recombination between distinct lyssaviruses. Recombination breakpoints were not linked to gene boundaries and could be detected all over the genome. However, there was no evidence that recombination is an important factor in the genetic variability of the rabies virus. It is therefore likely that recombination in the rabies virus is limited by ecological factors (e.g., rare co-circulation of distinguishable lineages and a narrow window for productive coinfection in most carnivore hosts), rather than molecular barriers (e.g., incompatibility of genome fragments).
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Публикация |
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Molecular and clinical aspects of embryotoxicity induced by acetylcholinesterase inhibitors
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Бурыкина Татьяна Ивановна
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Toxicology |
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Acetylcholinesterase inhibitors are widely used for a variety of medical, agricultural and public health purposes. Consequently, exposure is highly possible during lifetime. However, their systematic use raises concerns for the potential impact on the fetus and newborn since these substances may affect angiogenesis, the neonatal and maternal intensive care, neuroimmune function and response, mammary growth/lactation via cholinergic/non-cholinergic central and peripheral neuroendocrine pathways. New methodologies, neuroscientific technologies and research studies are needed to harness existing knowledge along with the proper management, availability for new acetylcholinesterase inhibitors, with stable pharmacodynamics and clinical outcomes.
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Публикация |
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Mesenchymal Stem Cell Therapy For Ischemic Heart Disease: Advances And Challenges
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Коноплянников Михаил Анатольевич
Котова Светлана Леонидовна
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Current Pharmaceutical Design |
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Ischemic Heart Disease (IHD) has been recognized as the main cause of mortality in the modern world. Application of cell therapy technologies for the IHD treatment has been actively studied from the beginning of 2000s. The review is dedicated to the use of mesenchymal stem cells (MSC) in the therapy of IHD. The strategies of the MSC modification in vitro for improvement of their regenerative potential are extensively discussed, including preconditioning to enhance the cell survival, boosting their paracrine effect and manipulating their cardiomyogenic differentiation. The optimization of the MSC delivery and opportunities related to the use of biomaterials as cell carriers are also discussed. The results of the most important clinical studies on the MSC-based IHD therapy are presented, including those completed and published in the literature and the ongoing clinical trials registered at clinicaltrials.gov by June 2018.
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Публикация |
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Role of a receptor-like kinase K1 in pea Rhizobium symbiosis development
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Порозов Юрий Борисович
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Planta |
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The LysM receptor-like kinase K1 is involved in regulation of pea-rhizobial symbiosis development.
The ability of the crop legume Pisum sativum L. to perceive the Nod factor rhizobial signals may depend on several receptors that differ in ligand structure specificity. Identification of pea mutants defective in two types of LysM receptor-like kinases (LysM-RLKs), SYM10 and SYM37, featuring different phenotypic manifestations and impaired at various stages of symbiosis development, corresponds well to this assumption. There is evidence that one of the receptor proteins involved in symbiosis initiation, SYM10, has an inactive kinase domain. This implies the presence of an additional component in the receptor complex, together with SYM10, that remains unknown. Here, we describe a new LysM-RLK, K1, which may serve as an additional component of the receptor complex in pea. To verify the function of K1 in symbiosis, several P. sativum non-nodulating mutants in the k1 gene were identified using the TILLING approach. Phenotyping revealed the blocking of symbiosis development at an appropriately early stage, strongly suggesting the importance of LysM-RLK K1 for symbiosis initiation. Moreover, the analysis of pea mutants with weaker phenotypes provides evidence for the additional role of K1 in infection thread distribution in the cortex and rhizobia penetration. The interaction between K1 and SYM10 was detected using transient leaf expression in Nicotiana benthamiana and in the yeast two-hybrid system. Since the possibility of SYM10/SYM37 complex formation was also shown, we tested whether the SYM37 and K1 receptors are functionally interchangeable using a complementation test. The interaction between K1 and other receptors is discussed.
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Публикация |
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How regularities of mortality statistics explain why we age despite having potentially ageless somatic stem cells
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Крутько Вячеслав Николаевич
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Biogerontology |
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Researchers working in the area of ageing have found numerous manifestations of this process at the molecular biological level, including DNA and protein damage, accumulation of metabolic by-products, lipids peroxidation, macromolecular cross-linking, non-enzymatic glycosylation, anti-oxidant/pro-oxidant misbalance, rising of pro-inflammatory cytokines, etc. This results in an increase in the proportion of cells in growth arrest, reduction of the rate of information processing, metabolic rate decrease, and decrease in rates of other processes characterizing dynamic aspects of the organism’s interaction with its environment. Such staggering multilevel diversity in manifestation of senescence precludes (without methodology of systems biology) development of a correct understanding of its primary causes and does not allow for developing approaches capable of postponing ageing or reducing organisms’ ageing rate to attain health preservation. Moreover, it turns out that damage production and damage elimination processes, the misbalance of which results in the ageing process, can to a large extent be regulated by external signals. The purpose of this report is to provide evidence supporting this view and its compatibility with the regularities of mortality statistics, because the main idea is very simple. Even potentially a non-senescent but certainly not immortal body must start to age under inadequate conditions (like a non-melting piece of ice taken out from the deepfreeze inevitably start to melt at the temperatures above zero Celsius). This conclusion is totally consistent with existing patterns of mortality and with agelessness potential of somatic stem cells. Therefore, there is no need to build up and explore too complicated, computational and sophisticated systems models of intrinsic ageing to understand the origin of this mainly extrinsic root cause of natural ageing, which is controlled by environmental signals. In our case, a simple phenomenological black-box approach with Input–Output analysis is ample. Here Input refers to the environmentally dependent initial force of mortality, whereas Output is a rate of age-related increase of mortality force.
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Публикация |
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Clinical implications of hepatitis b virus rna and covalently closed circular dna in monitoring patients with chronic hepatitis b today with a gaze into the future: The field is unprepared for a sterilizing cure
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Чуланов Владимир Петрович
Волочкова Елена Васильевна
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GENES |
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Chronic hepatitis B virus (HBV) infection has long remained a critical global health issue. Covalently closed circular DNA (cccDNA) is a persistent form of the HBV genome that maintains HBV chronicity. Decades of extensive research resulted in the two therapeutic options currently available: nucleot(s)ide analogs and interferon (IFN) therapy. A plethora of reliable markers to monitor HBV patients has been established, including the recently discovered encapsidated pregenomic RNA in serum, which can be used to determine treatment end-points and to predict the susceptibility of patients to IFN. Additionally, HBV RNA splice variants and cccDNA and its epigenetic modifications are associated with the clinical course and risks of hepatocellular carcinoma (HCC) and liver fibrosis. However, new antivirals, including CRISPR/Cas9, APOBEC-mediated degradation of cccDNA, and T-cell therapies aim at completely eliminating HBV, and it is clear that the diagnostic arsenal for defining the long-awaited sterilizing cure is missing. In this review, we discuss the currently available tools for detecting and measuring HBV RNAs and cccDNA, as well as the state-of-the-art in clinical implications of these markers, and debate needs and goals within the context of the sterilizing cure that is soon to come. View Full-Text
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Публикация |
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Peroxidase Activity of Human Hemoproteins: Keeping the Fire under Control
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Власова Ирина Ивановна
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Molecules |
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The heme in the active center of peroxidases reacts with hydrogen peroxide to form highly reactive intermediates, which then oxidize simple substances called peroxidase substrates. Human peroxidases can be divided into two groups: (1) True peroxidases are enzymes whose main function is to generate free radicals in the peroxidase cycle and (pseudo)hypohalous acids in the halogenation cycle. The major true peroxidases are myeloperoxidase, eosinophil peroxidase and lactoperoxidase. (2) Pseudo-peroxidases perform various important functions in the body, but under the influence of external conditions they can display peroxidase-like activity. As oxidative intermediates, these peroxidases produce not only active heme compounds, but also protein-based tyrosyl radicals. Hemoglobin, myoglobin, cytochrome c/cardiolipin complexes and cytoglobin are considered as pseudo-peroxidases. Рeroxidases play an important role in innate immunity and in a number of physiologically important processes like apoptosis and cell signaling. Unfavorable excessive peroxidase activity is implicated in oxidative damage of cells and tissues, thereby initiating the variety of human diseases. Hence, regulation of peroxidase activity is of considerable importance. Since peroxidases differ in structure, properties and location, the mechanisms controlling peroxidase activity and the biological effects of peroxidase products are specific for each hemoprotein. This review summarizes the knowledge about the properties, activities, regulations and biological effects of true and pseudo-peroxidases in order to better understand the mechanisms underlying beneficial and adverse effects of this class of enzymes. View Full-Text
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Публикация |
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HIBISCUS: Hydroxychloroquine for the secondary prevention of thrombotic and obstetrical events in primary antiphospholipid syndrome
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Макацария Александр Давидович
Бицадзе Виктория Омаровна
Хизроева Джамиля Хизриевна
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Autoimmunity Reviews |
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The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%–21% at 5 years in thrombotic APS and 20–28% in obstetrical APS [2, 3]. Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects [4–16]. Our group recently obtained the orphan designation of HCQ in antiphospholipid syndrome by the European Medicine Agency. Furthermore, the leaders of the project made the proposal of an international project, HIBISCUS, about the use of Hydroxychloroquine in secondary prevention of obstetrical and thrombotic events in primary APS. This study has been launched in several countries and at now, 53 centers from 16 countries participate to this international trial. This trial consists in two parts: a retrospective and a prospective study. The French part of the trial in thrombosis has been granted by the French Minister of Health in December 2015 (the academic trial independent of the pharmaceutical industry PHRC N PAPIRUS) and is coordinated by one of the members of the leading consortium of HIBISCUS.
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Публикация |
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Oncobox bioinformatical platform for selecting potentially effective combinations of target cancer drugs using high-throughput gene expression data
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Буздин Антон Александрович
Сорокин Максим Игоревич
Поддубская Елена Владимировна
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Cancers |
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Sequential courses of anticancer target therapy lead to selection of drug-resistant cells, which results in continuous decrease of clinical response. Here we present a new approach for predicting effective combinations of target drugs, which act in a synergistic manner. Synergistic combinations of drugs may prevent or postpone acquired resistance, thus increasing treatment efficiency. We cultured human ovarian carcinoma SKOV-3 and neuroblastoma NGP-127 cancer cell lines in the presence of Tyrosine Kinase Inhibitors (Pazopanib, Sorafenib, and Sunitinib) and Rapalogues (Temsirolimus and Everolimus) for four months and obtained cell lines demonstrating increased drug resistance. We investigated gene expression profiles of intact and resistant cells by microarrays and analyzed alterations in 378 cancer-related signaling pathways using the bioinformatical platform Oncobox. This revealed numerous pathways linked with development of drug resistant phenotypes. Our approach is based on targeting proteins involved in as many as possible signaling pathways upregulated in resistant cells. We tested 13 combinations of drugs and/or selective inhibitors predicted by Oncobox and 10 random combinations. Synergy scores for Oncobox predictions were significantly higher than for randomly selected drug combinations. Thus, the proposed approach significantly outperforms random selection of drugs and can be adopted to enhance discovery of new synergistic combinations of anticancer target drugs. View Full-Text Читать
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Публикация |
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A scientific methodology for expansion of anti-parkinson drug product range
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Пятигорская Наталья Валерьевна (Заместитель директора по научной работе)
Бркич Галина Эдуардовна (Руководитель центра)
Несвижский Юрий Владимирович (Профессор)
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Journal of Pharmaceutical Sciences and Research |
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A Scientific Methodology for Expansion of Anti-Parkinson Drug Product Range Nat a lia Valeryevna Pyatigorskaya Galina Eduardovna Brkich Alexey Nikitich Pavlov Valery Vasilyevich Beregovykh Olga Vladimirovna Evdokimova Sechenov First Moscow State Medical University, Russian Fedetation, 119991, Moscow, Trubetskaya Street, 8-2 Abstract Parkinson's disease (PD) is a chronic and progressive brain disease associat ed primarily with dopamine neurons degeneration of substantia nigra. More than 10 millions of people worldwide are affected by this disease manifested by combination of hypokinesia and rigidity, shaking, and postural instability. The high prevalence of disease has determined the aim of the study: to deve lop a methodology for expansion of anti-Parkinson drug product range. The information analysis methods were used for unbiased evaluation of novel anti-Parkinson drugs creation prospects. A systemic analysis of active pharmaceu tical ingredients (AFIs) used in anti- Parkinson drug products allowed for discovery of most widely used, levodopa being the top one. A comparative assessment of dosage forms used in Parkinson’s disease treatment showed th at they are represented primarily by intestinal gels, tablets, dispersible tablets, capsules, and modified release capsules. The authors conclude, that the novel anti-Parkinson drug pr oduct should contain levodopa in form of an endonasal spray which provides optimal bioavailability due to neces sary excipients (triglycerides, sodium monohydrogen phosphate, volatile and fatty oils, herbal extracts, stabilizers, and flavouring agents).
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Публикация |
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Indispensable Role of Proteases in Plant Innate Immunity
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Замятнин Андрей Александрович (директор)
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International Journal of Molecular Sciences |
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Plant defense is achieved mainly through the induction of microbe-associated molecular patterns (MAMP)-triggered immunity (MTI), effector-triggered immunity (ETI), systemic acquired resistance (SAR), induced systemic resistance (ISR), and RNA silencing. Plant immunity is a highly complex phenomenon with its own unique features that have emerged as a result of the arms race between plants and pathogens. However, the regulation of these processes is the same for all living organisms, including plants, and is controlled by proteases. Different families of plant proteases are involved in every type of immunity: some of the proteases that are covered in this review participate in MTI, affecting stomatal closure and callose deposition. A large number of proteases act in the apoplast, contributing to ETI by managing extracellular defense. A vast majority of the endogenous proteases discussed in this review are associated with the programmed cell death (PCD) of the infected cells and exhibit caspase-like activities. The synthesis of signal molecules, such as salicylic acid, jasmonic acid, and ethylene, and their signaling pathways, are regulated by endogenous proteases that affect the induction of pathogenesis-related genes and SAR or ISR establishment. A number of proteases are associated with herbivore defense. In this review, we summarize the data concerning identified plant endogenous proteases, their effect on plant-pathogen interactions, their subcellular localization, and their functional properties, if available, and we attribute a role in the different types and stages of innate immunity for each of the proteases covered. View Full-Text
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Публикация |
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Pro-neurogenic, Memory-Enhancing and Anti-stress Effects of DF302, a Novel Fluorine Gamma-Carboline Derivative with Multi-target Mechanism of Action
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Петер Леш (руководитель лаборатории Психиатрической Нейробиологии)
Стрекалова Т.В. ( зам руководителя лаборатории Психиатрической Нейробиологии)
Умрюхин А.T. (старший научный сотрудник)
Баженова Н.С. (младший научный сотрудник)
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Molecular Neurobiology |
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A comparative study performed in mice investigating the action of DF302, a novel fluoride-containing gamma-carboline derivative, in comparison to the structurally similar neuroprotective drug dimebon. Drug effects on learning and memory, emotionality, hippocampal neurogenesis and mitochondrial functions, as well as AMPA-mediated currents and the 5-HT6 receptor are reported. In the step-down avoidance and fear-conditioning paradigms, bolus administration of drugs at doses of 10 or 40 mg/kg showed that only the higher dose of DF302 improved long-term memory while dimebon was ineffective at either dosage. Short-term memory and fear extinction remained unaltered across treatment groups. During the 5-day predation stress paradigm, oral drug treatment over a period of 2 weeks at the higher dosage regimen decreased anxiety-like behaviour. Both compounds supressed inter-male aggression in CD1 mice, the most eminent being the effects of DF302 in its highest dose. DF302 at the higher dose decreased floating behaviour in a 2-day swim test and after 21-day ultrasound stress. The density of Ki67-positive cells, a marker of adult neurogenesis, was reduced in the dentate gyrus of stressed dimebon-treated and non-treated mice, but not in DF302-treated mice. Non-stressed mice that received DF302 had a higher density of Ki67-positive cells than controls unlike dimebon-treated mice. Similar to dimebon, DF302 effectively potentiated AMPA receptor-mediated currents, bound to the 5-HT6 receptor, inhibited mitochondrial permeability transition and displayed cytoprotective properties in cellular models of neurodegeneration. Thus, DF302 exerts multi-target effects on the key mechanisms of neurodegenerative pathologies and can be considered as an optimized novel analogue of the neuroprotective agent dimebon.
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тезис
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Recombination in the rabies virus and other lyssaviruses
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Девяткин Андрей Андреевич (старший научный сотрудник, лаборатория молекулярной биохимии)
Лукашев Александр Николаевич (Директор ФГБНУ ИПВЭ им.М.П.Чумакова, зав.лаб, НИИМПиТМ им.Е.И.Марциновского, Первого МГМУ им. И.М.Сеченова в.н.с.)
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Infection, Genetics and Evolution |
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Recombination is a common event in RNA viruses; however, in the rabies virus there have been only a few reports of isolated recombination events. Comprehensive analysis found traces of recent recombination events within Arctic, Arctic-like and Africa 1b rabies virus groups, as well as recombination between distinct lyssaviruses. Recombination breakpoints were not linked to gene boundaries and could be detected all over the genome. However, there was no evidence that recombination is an important factor in the genetic variability of the rabies virus. It is therefore likely that recombination in the rabies virus is limited by ecological factors (e.g., rare co-circulation of distinguishable lineages and a narrow window for productive coinfection in most carnivore hosts), rather than molecular barriers (e.g., incompatibility of genome fragments).
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